The proportion of CD161 on CD56⁺ NK cells in peripheral circulation associates with clinical features and disease activity of primary Sjögren's syndrome

Objectives: The purpose of this study was to examine the proportion of CD161 on CD56⁺ natural killer (NK) cells in peripheral blood of primary Sjögren's syndrome (pSS) and investigate its clinical relevance of pSS.

Methods: The proportion of CD56⁺ NK cells and CD161 on CD56⁺ NK cells was detected by flow cytometry in 31 pSS patients and 29 healthy controls (HCs). The correlations between the proportion of CD161⁺CD56⁺ NK cells and clinical features and disease activity of pSS were further analyzed. Meanwhile, we drew the receiver operating characteristic curve to evaluate the diagnostic value of CD161⁺CD56⁺ NK cells in pSS. In addition, we evaluated the differences in the effects of CD161⁺ cells and CD161^- cells in peripheral blood on the function of CD56⁺ NK cells in 5 pSS patients.

Results: The proportion of CD56⁺ NK cells and CD161⁺CD56⁺ NK cells decreased markedly in pSS patients compared to HCs. The correlation analysis showed that the proportion of CD161⁺CD56⁺ NK cells negatively correlated with white blood cells, Immunoglobulin A (IgA), IgM, IgG, European League Against Rheumatism Sjogren's Syndrome Patient Reported Index and European League Against Rheumatism Sjogren's Syndrome Disease Activity Index, and positively correlated with complement C4. The proportion of CD161⁺CD56⁺ NK cells in pSS patients with decayed tooth, fatigue, arthralgia, skin involvement, primary biliary cirrhosis, interstitial lung disease, anti-SSA/Ro60 positive, anti-SSB positive and high IgG was lower than that in negative patients. Furthermore, compared with inactive patients, the proportion of CD161⁺CD56⁺ NK cells decreased obviously in active patients. The area under the curve was 0.7375 (p = .0016), the results indicated that CD161⁺CD56⁺ NK cells had certain diagnostic values for pSS. In addition, the proportion of CD86, HLA-DR, Ki67, FasL, TNF-α, and IFN-γ on CD161⁺CD56⁺ NK cells was lower than that on CD161^-CD56⁺ NK cells in the peripheral blood of pSS patients.

Conclusion: This study suggested that the proportion of CD56⁺ NK cells and CD161⁺CD56⁺ NK cells decreased significantly in pSS patients, and the proportion of CD161⁺CD56⁺ NK cells negatively associated with the clinical features and disease activity of pSS patients. CD161 expression inhibited the function of CD56⁺ NK cells in peripheral blood of pSS patients. The CD161⁺CD56⁺ NK cells may present as a potential target for therapy and a biomarker of disease activity in pSS.